Selective induction of de novo prostaglandin biosynthesis in rabbit kidney cortex.
Ureter-obstructed kidney develops during perfusion an enhanced responsiveness to bradykinin-stimulated prostaglandin release. This enhanced prostaglandin generation results from de novo synthesis of prostaglandin synthetase and acylhydrolase enzymes during the perfusion and is therefore unaffected by acetylsalicylic acid (aspirin) inhibition of prostaglandin synthesis prior to initiation of perfusion. Studies were carried out to identify the renal cellular site in which the newly synthesizing prostaglandin generating system is localized. Kidneys with or without aspirin treatment were perfused for either 1 or 5 h. Following perfusion, medullary and cortical slices were incubated and prostaglandin E2 production measured. Medullary slices showed similar prostaglandin E2 biosynthetic activity in kidneys perfused for 1 or 5 h. Furthermore, medullary prostaglandin generation was inhibited (90-95%) by aspirin pre-treatment and did not increase during subsequent perfusion for 5 h. In contrast, cortical slices from kidneys pretreated with aspirin regained their full activity after 5 h or perfusion, this regeneration being abolished by infusion of the protein synthesis inhibitor, cycloheximide. The same differences in activities between medulla and cortex were also seen when microsomal fractions were compared. The perfusion-induced formation of prostaglandin synthetase activity is thus specifically localized in the cortex and can be detected in cortical microsomes. This cortical activity is unique in that endogenous arachidonic acid released from esterified lipids is converted to prostaglandins, whereas exogenous added arachidonic acid is not. It thus appears that the induced cortical acylhydrolase and prostaglandin synthetase activities are tightly coupled and that the true molecular form or precursor arachidonate for this prostaglandin generating system is esterified and not free arachidonate.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011458:Prostaglandins E / Q000096:biosynthesis*; D011817:Rabbits; D014517:Ureteral Obstruction / Q000378:metabolism
D011458:Prostaglandins E; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D001920:Bradykinin